The purpose of this project is to examine in depth the cause of the impaired carbohydrate tolerance in peripheral and insulin resistance which commonly occur in uremia. An attempt is being made to correlate alterations in carbohydrate, protein, and lipid metabolism in uremia in light of recent knowledge of the roles of insulin, growth hormone, and glucogon in the regulation of intermediary metabolism. Factors affecting peripheral insulin resistance are being studied using the forearm perfusion technique, and the hypothesis that the abnormal carbohydrate metabolism in uremia may be a metabolic adaptation to chronic protein depletion rather than due to a specific uremic toxin is being examined in patients with chronic renal failure who are being studied at the Clinical Research Center at the University of Vermont. Patients are stabilized on either high or low protein diets with carbohydrate and total calories being maintained constant. Patients are also studied before and after intensive hemodialysis while maintaining protein intake constant. Carbohydrate tolerance, insulin and growth hormone responses, forearm metabolism, plasma amino acid patterns, plasma lipid patterns, and biochemical parameters of renal function are being monitored under the various conditions. An attempt is being made to dissociate the affects of hemodialysis from the affects of altered protein content of the diet.